Using α radiation to boost cancer immunity?
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ABSTRACT:
SUBMITTER: Gorin JB
PROVIDER: S-EPMC4292714 | biostudies-other | 2014 Oct
REPOSITORIES: biostudies-other
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Project description:PurposeTo test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer.Methods and materialsWeekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2).ResultsThe 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase.ConclusionsThe tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.
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Project description:This proof-of-concept study investigates the immune effects in metastatic breast cancer (MBC) patients after "vaccination" with activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2 BATs) followed by immune consolidation with immune ATC "boost" after high dose chemotherapy (HDC) and autologous stem cell transplant (SCT). Approximately 2 weeks after completion of vaccination portion of the study, immune T cells were obtained by leukopheresis, activated and expanded ex vivo and re-infused after HDC and SCT to test the hypothesis that transfer of immune unarmed ATC would accelerate reconstitution of anti-tumor activity after SCT. Eight metastatic breast cancer (MBC) patients received 8 infusions of HER2 BATs, low dose IL-2, and GM-CSF in the first part of the protocol to induce adaptive cellular and humoral responses. In the "boost" portion of the protocol, 6 of 8 patients received multiple infusions of unarmed ATC post SCT. There were no dose-limiting toxicities or delays in engraftment. Four of 6 patients tested for the immune correlative studies exhibited increases in anti-breast cancer (BrCa) cytotoxicity, antigen specific IFN-? Elispots, anti-BrCa antibodies and increased IL-12 and Th1 serum cytokine levels after HER2 BATs infusions. Anti-BrCa tumor responses were seen as early as 2 weeks after SCT and persisted up to 2 years post-SCT. One out of 6 patients' rapidly progressed and showed poor immune responses and high Th2 cytokine levels. There was a significant correlation (p < 0.002) between time to progression (TTP) and anti-BrCa cytotoxicity by immune T cells. This is the first study to show that adoptive transfer of immune T cells after SCT accelerates reconstitution of anti-BrCa specific immunity and correlates with delay TTP.
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Project description:PurposeTo provide a detailed description of practical approaches to dose escalation in pancreatic cancer.Methods and materialsThe current paper represents an international collaborative effort of radiation oncologists from the MR-linac consortium with expertise in pancreatic dose escalation.ResultsA 15-fraction hypofractionated intensity modulated radiation therapy (67.5 Gy in 15 fractions) and 5-fraction stereotactic body radiation therapy case (50 Gy in 5 fractions) are presented with information regarding patient selection, target volumes, organs at risk, dose constraints, and specific considerations regarding quality assurance. Additionally, we address barriers to dose escalation and briefly discuss future directions in dose escalation for pancreatic cancer, including particle therapy and magnetic resonance guided radiation therapy.ConclusionsThis article on dose escalation for pancreatic cancer may help to guide academic and community based physicians and to serve as a reference for future therapeutic trials.
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Project description:Intradermal rabies vaccine is recommended by the World Health Organisation, but not all countries, including England, follow this recommendation. A group of 12 adults in England previously given pre-exposure intradermal rabies vaccine were considered to be non-immune to rabies because their rabies antibody titres were known to be less than 0.5?IU/mL. A cohort study examined the immunizing effect of increasing the participants' cumulative dose of intradermal rabies to 2.0?IU. All patients subsequently demonstrated rabies antibody levels >0.5?IU·mL supporting evidence of adequate sero-conversion. No adverse effects of intradermal rabies vaccine boosting were noted. Within the limits of a small study the findings support the hypothesis that adequate levels of rabies antibody can be achieved by a schedule of intradermal injections delivered on at least three occasions with a cumulative rabies vaccine dose of 2.0?IU.
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Project description:BackgroundRadiation therapy and chemoradiation therapy play a major role in the definitive management of esophageal cancer. Survival in esophageal cancer patients is still relatively poor, mostly due to high rates of local recurrence and distant metastases. It is hypothesized that dose escalation in radiotherapy could improve outcomes. Therefore, this retrospective analysis aimed to investigate the outcomes and toxicity in patients treated with local dose escalation by means of using simultaneous integrated boost concepts.MethodsBetween 2012 and 2018, 101 patients with esophageal carcinoma were analyzed in this monocentric, retrospective study. All patients received definitive chemoradiation or radiation therapy alone as intensity modulated radiotherapy. The prescribed dose was 50.4 Gy in 28 fractions to the primary tumor and the elective lymph nodes as well as a simultaneous integrated boost (SIB) with 58.8 Gy to macroscopic tumor and lymph node metastases. Endpoints were overall survival (OS), progression free survival (PFS), local control rate (LCR) and toxicity.Results60 patients (59.4%) received chemoradiation, 41 patients (40.6%) radiotherapy alone. The median follow up was 17 months (range 0-75 months). OS, PFS and LCR were at 63.9%, 53.9% and 59.9% after 1 year and 37.6%, 34.5% and 36.1%, respectively after 3 years. 16 patients (15.8%) in total developed a locoregional recurrence within the field of radiation. In 48 patients (47.5%) at least one grade III° (CTCAE) toxicity was documented during radiotherapy, mostly dysphagia (36 pat., 75%). One patient suffered from a grade IV° pneumonia.ConclusionThis retrospective analysis demonstrates that a SIB concept in definitive (chemo)radiation therapy is safe and feasible, showing acceptable outcomes in this patient cohort. Considering that this cohort mainly consists of elderly patients not eligible for chemotherapy in many cases, we emphasize the aspect of SIB radiation therapy as potential partial compensation for omitted simultaneous chemotherapy. Prospective studies are needed for validation.
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